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Tacrolimus-based immunossupression favours liver regeneration induced by extent hepatectomy in rats

BACKGROUND: Liver regeneration is the result of physiological responses that occur after loss of parenchyma, as a consequence of drug abuse-toxic, infection, trauma or surgical procedure. AIM: To analyze, during two different moments of liver regeneration, the effect of the immunosuppressant tacrolimus on the 70% hepatectomy model-induced liver regeneration in adult rats. METHODS: Forty Wistar adult rats, weighing 510.08+11.66 g were randomly divided into two groups (Study or Control), each group divided into two subgroups according to the death day after 70% hepatectomy (24 hours or 7 days). According to the group of study, rats received 0.1mg/Kg/day of tacrolimus or the same volume of saline solution, by gavage, daily, starting three days before hepatectomy until the end of observation (animal death´s day). After three days of pre-therapy, all animals were submitted to 70% hepatectomy by resection of median and left lateral hepatic lobes which were weighed for posterior calculation of liver regeneration by Kwon´s formula. Twenty four hours or seven days after hepatectomy 10 rats of each group were killed; the remaining liver (regenerated) was entirely resected, weighed and sampled for mitotic index on hematoxylin-eosin staining and immunohistochemical assays with PCNA and Ki-67 markers. Data were statistically analyzed by Mann-Whitney or Student "t" tests, with significance level of 5% (P<0.05). RESULTS: Rats receiving tacrolimus showed statistically significant higher levels of liver regeneration when compared to placebo according to Kwon's formula, mitotic index and PCNA marker. Identical trend was found with Ki-67 marker, but without statistical significance. CONCLUSION: Tacrolimus-based immunossuppression has stimulatory effect on liver regeneration process induced by 70% hepatectomy in adult Wistar rats.

Tacrolimus; Hepatectomy; Liver regeneration


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